FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Nature reviews. Disease primers2025; 11(1); 32; doi: 10.1038/s41572-025-00614-5

Leptospirosis.

Abstract: Leptospirosis is a zoonotic bacterial infection that is prevalent across all continents and is caused by pathogenic spirochaetes of the genus Leptospira. Although infection can be asymptomatic, symptomatic disease can vary in severity from mild to severe illness, the latter characterized by icterus and/or multi-organ dysfunction and potentially death. An estimated one million cases of leptospirosis occur globally each year, resulting in ~60,000 deaths. The pathogenesis of severe leptospirosis is poorly understood but is believed to involve an interplay between genetic predisposition, pathogen virulence and dysregulated immune responses that trigger a cytokine storm with associated immunoparesis. Leptospira are susceptible to several low-cost antibiotics, including benzyl penicillin, doxycycline, cephalosporins and macrolides, when used in the early phase of infection. Late disease with organ dysfunction is treated with supportive care, and the benefit of antibiotics during late disease is doubtful. Very few countries have licensed a vaccine for human leptospirosis, and available vaccines only protect against rodent-associated serogroups. Exposure control by behavioural modifications and personal protective measures are the major preventative measures in leptospirosis, and the efficacy of prophylactic antibiotics has not been confirmed in clinical trials. Future research is needed to accurately estimate leptospirosis disease burden across the globe, to understand the pathophysiology of severe leptospirosis to inform the design of targeted immunotherapies and vaccines, and to develop cost-effective and accurate point-of-care diagnostics.
© 2025. Springer Nature Limited.
Get Full Text
Publication Date: 2025-05-02 PubMed ID: 40316520PubMed Central: 4442676DOI: 10.1038/s41572-025-00614-5Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Review

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article primarily discusses the connection between the disease Leptospirosis and ocular changes in horses, including the recurrent sequelae of these changes. The research also explores the more recent increase in reports of equine abortion, stillbirth, and neonatal disease associated with this infection and potential treatments to be used.

Disease and its effects

  • The research starts by discussing how clinical leptospirosis in horses is primarily connected to changes in the horse’s eyes, more specifically uveitis and recurrent sequelae, or the aftereffects of these ocular changes. Sequelae are typically pathological conditions resulting from a disease or injury.
  • While there have been sporadic reports of kidney and liver involvement in horses due to this disease, these are less common.

Emerging Concerns

  • In recent times, a type of leptospira called serovar bratislava has been found to be adapted in horses, which is significant for the study of the disease in this species.
  • Reports on equine abortion and stillbirth have become more frequent. This frequency is likely due to improved diagnostic techniques, rather than a rise in the disease itself.
  • Particularly noteworthy is the increasing recognition of equine neonatal disease circumstance associated with leptospira infection.
  • Whether the infection causes abortion or affects foals (young horses) may depend on the stage of gestation when the mare is exposed and the immune status of the host (the mare, in this case).

Treatment Options

  • The article then moves onto discussing the treatment options for this condition. The choice of antibiotic for treating equine leptospirosis is uncertain because specific studies focused on equine have not yet been conducted.
  • That said, treatments used for other species suggest that streptomycin might be a good therapeutic choice for the chronic shedding state (where the bacteria is persistently released in the urine).
  • Streptomycin may also be used in combination with other antimicrobials for treating acute (short-term but severe) disease.
  • Furthermore, Penicillins (specifically potentiated ones) and tetracycline might be logical choices for treating acute leptospirosis, provided they are given in the appropriate or high-end dosages.

Cite This Article

APA
Rajapakse S, Fernando N, Dreyfus A, Smith C, Rodrigo C. (2025). Leptospirosis. Nat Rev Dis Primers, 11(1), 32. https://doi.org/10.1038/s41572-025-00614-5

Publication

Nature reviews. Disease primers
ISSN: 2056-676X
NlmUniqueID: 101672103
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 32

Researcher Affiliations

Rajapakse, Senaka
  • Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka. senaka@med.cmb.ac.lk.
Fernando, Narmada
  • Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka.
Dreyfus, Anou
  • Section of Epidemiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Smith, Chris
  • Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
  • School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
Rodrigo, Chaturaka
  • Department of Pathology, School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.

MeSH Terms

  • Humans
  • Leptospirosis / epidemiology
  • Leptospirosis / physiopathology
  • Leptospirosis / diagnosis
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Bacterial Agents / pharmacology
  • Animals
  • Leptospira / pathogenicity

Conflict of Interest Statement

Competing interests: The authors declare no competing interests.

References

This article includes 249 references
  1. European Centre for Disease Prevention and Control. Factsheet about leptospirosis. 2017.
  2. Haake DA, Levett PN. Leptospirosis in humans. Curr. Top. Microbiol. Immunol. 387, 65–97 (2015).
    pubmed: 25388133pmc: 4442676
  3. Bolin CA, Koellner P. Human-to-human transmission of Leptospira interrogans by milk. J. Infect. Dis. 158, 246–247 (1988).
    pubmed: 3392418doi: 10.1093/infdis/158.1.246google scholar: lookup
  4. Carles G, Montoya E, Joly F, Peneau C. Leptospirosis and pregnancy. Eleven cases in French Guyana. J. Gynecol. Obstet. Biol. Reprod. 24, 418–421 (1995).
  5. Evangelista KV, Coburn J. Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses. Future Microbiol. 5, 1413–1425 (2010).
    pubmed: 20860485doi: 10.2217/fmb.10.102google scholar: lookup
  6. Raddi G et al. Three-dimensional structures of pathogenic and saprophytic leptospira species revealed by cryo-electron tomography. J. Bacteriol. 194, 1299–1306 (2012).
    pubmed: 22228733pmc: 3294836doi: 10.1128/JB.06474-11google scholar: lookup
  7. Vincent AT et al. Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics. PLoS Negl. Trop. Dis. 13, e0007270 (2019).
    pubmed: 31120895pmc: 6532842doi: 10.1371/journal.pntd.0007270google scholar: lookup
  8. Kędzierska-Mieszkowska S. Sigma factors of RNA polymerase in the pathogenic spirochaete Leptospira interrogans, the causative agent of leptospirosis. FASEB J. 37, e23163 (2023).
    pubmed: 37688587doi: 10.1096/fj.202300252RRRgoogle scholar: lookup
  9. Guglielmini J et al. Genus-wide Leptospira core genome multilocus sequence typing for strain taxonomy and global surveillance. PLoS Negl. Trop. Dis. 13, e0007374 (2019).
    pubmed: 31026256pmc: 6513109doi: 10.1371/journal.pntd.0007374google scholar: lookup
  10. Costa F et al. Global morbidity and mortality of leptospirosis: a systematic review. PLoS Negl. Trop. Dis. 9, e0003898 (2015).
    pubmed: 26379143pmc: 4574773doi: 10.1371/journal.pntd.0003898google scholar: lookup
  11. Weil A. Ueber einer eigenhuemliche, mit milztumor, icterus un nephritis einhergehende, acute infektionskrankheit. Deutsch Arch. Klin. Med. 109, 209–232 (1886).
  12. Clemente BM, Pineda-Cortel MR, Villaflores O. Evaluating immunochromatographic test kits for diagnosis of acute human leptospirosis: a systematic review. Heliyon 8, e11829 (2022).
    pubmed: 36458294pmc: 9706160doi: 10.1016/j.heliyon.2022.e11829google scholar: lookup
  13. Limmathurotsakul D et al. Fool’s gold: why imperfect reference tests are undermining the evaluation of novel diagnostics: a reevaluation of 5 diagnostic tests for leptospirosis. Clin. Infect. Dis. 55, 322–331 (2012).
    pubmed: 22523263pmc: 3393707doi: 10.1093/cid/cis403google scholar: lookup
  14. Rajapakse S, Rodrigo C, Handunnetti SM, Fernando SD. Current immunological and molecular tools for leptospirosis: diagnostics, vaccine design, and biomarkers for predicting severity. Ann. Clin. Microbiol. Antimicrob. 14, 2 (2015).
    pubmed: 25591623pmc: 4299796doi: 10.1186/s12941-014-0060-2google scholar: lookup
  15. Boss J et al. Antimicrobial susceptibility testing of leptospira spp. in the Lao People’s Democratic Republic using disk diffusion. Am. J. Trop. Med. Hyg. 100, 1073–1078 (2019).
    pubmed: 30887950pmc: 6493943doi: 10.4269/ajtmh.18-0955google scholar: lookup
  16. Chawla V, Trivedi TH, Yeolekar ME. Epidemic of leptospirosis: an ICU experience. J. Assoc. Physicians India 52, 619–622 (2004).
    pubmed: 15847354
  17. Levett PN. Leptospirosis. Clin. Microbiol. Rev. 14, 296–326 (2001).
    pubmed: 11292640pmc: 88975doi: 10.1128/CMR.14.2.296-326.2001google scholar: lookup
  18. Bharti AR et al. Leptospirosis: a zoonotic disease of global importance. Lancet Infect. Dis. 3, 757–771 (2003).
    pubmed: 14652202doi: 10.1016/S1473-3099(03)00830-2google scholar: lookup
  19. Munoz-Zanzi C et al. A systematic literature review of leptospirosis outbreaks worldwide, 1970–2012. Rev. Panam. Salud Publica 44, e78 (2020).
    pubmed: 32684917pmc: 7363284doi: 10.26633/RPSP.2020.78google scholar: lookup
  20. Zeng Z, Zhan J, Chen L, Chen H, Cheng S. Global, regional, and national dengue burden from 1990 to 2017: a systematic analysis based on the global burden of disease study 2017. eClinicalMedicine 2021.
    doi: 10.1016/j.eclinm.2020.100712google scholar: lookup
  21. Allan KJ et al. Epidemiology of leptospirosis in Africa: a systematic review of a neglected zoonosis and a paradigm for ‘One Health’ in Africa. PLoS Negl. Trop. Dis. 9, e0003899 (2015).
    pubmed: 26368568pmc: 4569256doi: 10.1371/journal.pntd.0003899google scholar: lookup
  22. Gizamba JM, Mugisha L. Leptospirosis in humans and selected animals in sub-Saharan Africa, 2014–2022: a systematic review and meta-analysis. BMC Infect. Dis. 23, 649 (2023).
    pubmed: 37784071pmc: 10546638doi: 10.1186/s12879-023-08574-5google scholar: lookup
  23. Beauté J et al. Epidemiology of reported cases of leptospirosis in the EU/EEA, 2010 to 2021. Euro Surveill. 2024.
    doi: 10.2807/1560-7917.es.2024.29.7.2300266google scholar: lookup
  24. Lau CL, Smythe LD, Craig SB, Weinstein P. Climate change, flooding, urbanisation and leptospirosis: fuelling the fire?. Trans. R. Soc. Trop. Med. Hyg. 104, 631–638 (2010).
    pubmed: 20813388doi: 10.1016/j.trstmh.2010.07.002google scholar: lookup
  25. Cann KF, Thomas DR, Salmon RL, Wyn-Jones AP, Kay D. Extreme water-related weather events and waterborne disease. Epidemiol. Infect. 141, 671–686 (2013).
    pubmed: 22877498doi: 10.1017/S0950268812001653google scholar: lookup
  26. Baharom M et al. Environmental and occupational factors associated with leptospirosis: a systematic review. Heliyon 10, e23473 (2024).
    pubmed: 38173528doi: 10.1016/j.heliyon.2023.e23473google scholar: lookup
  27. Mwachui MA, Crump L, Hartskeerl R, Zinsstag J, Hattendorf J. Environmental and behavioural determinants of leptospirosis transmission: a systematic review. PLoS Negl. Trop. Dis. 9, e0003843 (2015).
    pubmed: 26379035pmc: 4574979doi: 10.1371/journal.pntd.0003843google scholar: lookup
  28. Hartskeerl RA, Collares-Pereira M, Ellis WA. Emergence, control and re-emerging leptospirosis: dynamics of infection in the changing world. Clin. Microbiol. Infect. 17, 494–501 (2011).
    pubmed: 21414083doi: 10.1111/j.1469-0691.2011.03474.xgoogle scholar: lookup
  29. Hagedoorn NN et al. Global distribution of Leptospira serovar isolations and detections from animal host species: a systematic review and online database. Trop. Med. Int. Health 29, 161–172 (2024).
    pubmed: 38351504pmc: 11076152doi: 10.1111/tmi.13965google scholar: lookup
  30. Allan KJ et al. Assessment of animal hosts of pathogenic Leptospira in northern Tanzania. PLoS Negl. Trop. Dis. 12, e0006444 (2018).
    pubmed: 29879104pmc: 5991636doi: 10.1371/journal.pntd.0006444google scholar: lookup
  31. Chadsuthi S et al. Investigation on predominant Leptospira serovars and its distribution in humans and livestock in Thailand, 2010–2015. PLoS Negl. Trop. Dis. 11, e0005228 (2017).
    pubmed: 28182662pmc: 5325611doi: 10.1371/journal.pntd.0005228google scholar: lookup
  32. Casanovas-Massana A et al. Genetic evidence for a potential environmental pathway to spillover infection of rat-borne leptospirosis. J. Infect. Dis. 225, 130–134 (2022).
    pubmed: 34139761doi: 10.1093/infdis/jiab323google scholar: lookup
  33. Faine S, Adler B, Bolin C, Perolat P. Leptospira and Leptospirosis Vol. 2. 1999.
  34. Adler B, de la Pena Moctezuma A. Leptospira and leptospirosis. Vet. Microbiol. 140, 287–296 (2010).
    pubmed: 19345023doi: 10.1016/j.vetmic.2009.03.012google scholar: lookup
  35. Bierque E, Thibeaux R, Girault D, Soupé-Gilbert M-E, Goarant C. A systematic review of Leptospira in water and soil environments. PLoS ONE 15, e0227055 (2020).
    pubmed: 31986154pmc: 6984726doi: 10.1371/journal.pone.0227055google scholar: lookup
  36. Thibeaux R et al. Seeking the environmental source of Leptospirosis reveals durable bacterial viability in river soils. PLoS Negl. Trop. Dis. 11, e0005414 (2017).
    pubmed: 28241042pmc: 5344526doi: 10.1371/journal.pntd.0005414google scholar: lookup
  37. Hacker KP et al. Influence of rainfall on leptospira infection and disease in a tropical urban setting, Brazil. Emerg. Infect. Dis. 26, 311–314 (2020).
    pubmed: 31961288pmc: 6986844doi: 10.3201/eid2602.190102google scholar: lookup
  38. Rodríguez-Rodríguez V et al. Acute human leptospirosis in a Caribbean region of Colombia: from classic to emerging risk factors. Zoonoses Public Health 71, 107–119 (2024).
    pubmed: 37924220doi: 10.1111/zph.13089google scholar: lookup
  39. Susanna D, Nova RIT, Rozek L. Community behaviors that affect the incidence of leptospirosis in West Jakarta, Indonesia. Vector Borne Zoonotic Dis. 23, 29–34 (2023).
    pubmed: 36508276doi: 10.1089/vbz.2022.0023google scholar: lookup
  40. Amilasan AS et al. Outbreak of leptospirosis after flood, the Philippines, 2009. Emerg. Infect. Dis. 18, 91–94 (2012).
    pubmed: 22257492pmc: 3310081doi: 10.3201/eid1801.101892google scholar: lookup
  41. Sanders EJ et al. Increase of leptospirosis in dengue-negative patients after a hurricane in Puerto Rico in 1996 (correction of 1966). Am. J. Trop. Med. Hyg. 61, 399–404 (1999).
    pubmed: 10497979doi: 10.4269/ajtmh.1999.61.399google scholar: lookup
  42. Dreesman J et al. Investigation and response to a large outbreak of leptospirosis in field workers in Lower Saxony, Germany. Zoonoses Public Health 70, 315–326 (2023).
    pubmed: 36692076doi: 10.1111/zph.13027google scholar: lookup
  43. Dreyfus A et al. Risk factors for new infection with Leptospira in meat workers in New Zealand. Occup. Environ. Med. 72, 219–225 (2015).
    pubmed: 25520373doi: 10.1136/oemed-2014-102457google scholar: lookup
  44. Pagès F et al. Investigation of a leptospirosis outbreak in triathlon participants, Réunion Island, 2013. Epidemiol. Infect. 144, 661–669 (2016).
    pubmed: 26211921doi: 10.1017/S0950268815001740google scholar: lookup
  45. Bradley EA, Lockaby G. Leptospirosis and the environment: a review and future directions. Pathogens 2023.
    doi: 10.3390/pathogens12091167google scholar: lookup
  46. Magalhães AR et al. Neglected tropical diseases risk correlates with poverty and early ecosystem destruction. Infect. Dis. Poverty 12, 32 (2023).
    pubmed: 37038199pmc: 10084676doi: 10.1186/s40249-023-01084-1google scholar: lookup
  47. Jeffree MS et al. High incidence of asymptomatic leptospirosis among urban sanitation workers from Kota Kinabalu, Sabah, Malaysian Borneo. Sci. Rep. 10, 19442 (2020).
    pubmed: 33173153pmc: 7655852doi: 10.1038/s41598-020-76595-0google scholar: lookup
  48. Khalil H et al. Poverty, sanitation, and Leptospira transmission pathways in residents from four Brazilian slums. PLoS Negl. Trop. Dis. 15, e0009256 (2021).
    pubmed: 33788864pmc: 8041187doi: 10.1371/journal.pntd.0009256google scholar: lookup
  49. Reis RB et al. Impact of environment and social gradient on Leptospira infection in urban slums. PLoS Negl. Trop. Dis. 2, e228 (2008).
    pubmed: 18431445pmc: 2292260doi: 10.1371/journal.pntd.0000228google scholar: lookup
  50. Antima, Banerjee S. Modeling the dynamics of leptospirosis in India. Sci. Rep. 13, 19791 (2023).
    pubmed: 37957218pmc: 10643689doi: 10.1038/s41598-023-46326-2google scholar: lookup
  51. Lingappa J et al. HLA-DQ6 and ingestion of contaminated water: possible gene–environment interaction in an outbreak of Leptospirosis. Genes Immun. 5, 197–202 (2004).
    pubmed: 15014429doi: 10.1038/sj.gene.6364058google scholar: lookup
  52. Agampodi SB, Matthias MA, Moreno AC, Vinetz JM. Utility of quantitative polymerase chain reaction in leptospirosis diagnosis: association of level of leptospiremia and clinical manifestations in Sri Lanka. Clin. Infect. Dis. 54, 1249–1255 (2012).
    pubmed: 22354922pmc: 3404689doi: 10.1093/cid/cis035google scholar: lookup
  53. Cagliero J, Villanueva S, Matsui M. Leptospirosis pathophysiology: into the storm of cytokines. Front. Cell. Infect. Microbiol. 8, 204 (2018).
    pubmed: 29974037pmc: 6019470doi: 10.3389/fcimb.2018.00204google scholar: lookup
  54. Nicodemo AC et al. Lung lesions in human leptospirosis: microscopic, immunohistochemical, and ultrastructural features related to thrombocytopenia. Am. J. Trop. Med. Hyg. 56, 181–187 (1997).
    pubmed: 9080878doi: 10.4269/ajtmh.1997.56.181google scholar: lookup
  55. Chierakul W et al. Activation of the coagulation cascade in patients with leptospirosis. Clin. Infect. Dis. 46, 254–260 (2008).
    pubmed: 18171258doi: 10.1086/524664google scholar: lookup
  56. Yücel Koçak S, Kudu A, Kayalar A, Yilmaz M, Apaydin S. Leptospirosis with acute renal failure and vasculitis: a case report. Arch. Rheumatol. 34, 229–232 (2019).
    pubmed: 31497771doi: 10.5606/ArchRheumatol.2019.7063google scholar: lookup
  57. De Brito T, Silva A, Abreu PAE. Pathology and pathogenesis of human leptospirosis: a commented review. Rev. Inst. Med. Trop. Sao Paulo 60, e23 (2018).
    pubmed: 29846473pmc: 5975557doi: 10.1590/s1678-9946201860023google scholar: lookup
  58. Shintaku M, Itoh H, Tsutsumi Y. Weil’s disease (leptospirosis) manifesting as fulminant hepatic failure: report of an autopsy case. Pathol. Res. Pract. 210, 1134–1137 (2014).
    pubmed: 24997567doi: 10.1016/j.prp.2014.05.002google scholar: lookup
  59. Arean VM. The pathologic anatomy and pathogenesis of fatal human leptospirosis (Weil’s disease). Am. J. Pathol. 40, 393–423 (1962).
    pubmed: 13862141pmc: 1949541
  60. Sitprija V, Evans H. The kidney in human leptospirosis. Am. J. Med. 49, 780–788 (1970).
    pubmed: 5006616doi: 10.1016/S0002-9343(70)80059-6google scholar: lookup
  61. Abdulkader RC, Silva MV. The kidney in leptospirosis. Pediatr. Nephrol. 23, 2111–2120 (2008).
    pubmed: 18446381doi: 10.1007/s00467-008-0811-4google scholar: lookup
  62. Dolhnikoff M, Mauad T, Bethlem EP, Carvalho CR. Pathology and pathophysiology of pulmonary manifestations in leptospirosis. Braz. J. Infect. Dis. 11, 142–148 (2007).
    pubmed: 17625743doi: 10.1590/S1413-86702007000100029google scholar: lookup
  63. Fernando T et al. Electrocardiographic and echocardiographic manifestations of cardiac involvement in leptospirosis. Trans. R. Soc. Trop. Med. Hyg. 107, 457–459 (2013).
    pubmed: 23732365doi: 10.1093/trstmh/trt038google scholar: lookup
  64. Swarath S et al. Leptospirosis-induced myocarditis and arrhythmias. J. Investig. Med. High. Impact Case Rep. 11, 23247096231179450 (2023).
    pubmed: 37287275pmc: 10262647doi: 10.1177/23247096231179450google scholar: lookup
  65. Silva JJ et al. Clinicopathological and immunohistochemical features of the severe pulmonary form of leptospirosis. Rev. Soc. Bras. Med. Trop. 35, 395–399 (2002).
    pubmed: 12170336doi: 10.1590/S0037-86822002000400017google scholar: lookup
  66. Cédola M et al. Association of Toll-like receptor 2 Arg753Gln and Toll-like receptor 1 Ile602Ser single-nucleotide polymorphisms with leptospirosis in an Argentine population. Acta Trop. 146, 73–80 (2015).
    pubmed: 25784560doi: 10.1016/j.actatropica.2015.03.007google scholar: lookup
  67. Viriyakosol S, Matthias MA, Swancutt MA, Kirkland TN, Vinetz JM. Toll-like receptor 4 protects against lethal Leptospira interrogans serovar icterohaemorrhagiae infection and contributes to in vivo control of leptospiral burden. Infect. Immun. 74, 887–895 (2006).
    pubmed: 16428731pmc: 1360355doi: 10.1128/IAI.74.2.887-895.2006google scholar: lookup
  68. Haake DA, Zückert WR. Spirochetal lipoproteins in pathogenesis and immunity. Curr. Top. Microbiol. Immunol. 415, 239–271 (2018).
    pubmed: 29196824
  69. Li D, Wu M. Pattern recognition receptors in health and diseases. Signal. Transduct. Target. Ther. 6, 291 (2021).
    pubmed: 34344870pmc: 8333067doi: 10.1038/s41392-021-00687-0google scholar: lookup
  70. Senavirathna I, Rathish D, Agampodi S. Cytokine response in human leptospirosis with different clinical outcomes: a systematic review. BMC Infect. Dis. 20, 268 (2020).
    pubmed: 32264832pmc: 7137275doi: 10.1186/s12879-020-04986-9google scholar: lookup
  71. Wang H et al. Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-κB signaling pathways. PLoS ONE 7, e42266 (2012).
    pubmed: 22870312pmc: 3411626doi: 10.1371/journal.pone.0042266google scholar: lookup
  72. Reis EA et al. Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis. PLoS Negl. Trop. Dis. 7, e2457 (2013).
    pubmed: 24069500pmc: 3777885doi: 10.1371/journal.pntd.0002457google scholar: lookup
  73. Nisansala T et al. Contributing role of TNF, IL-10, sTNFR1 and TNF gene polymorphisms in disease severity of leptospirosis. Med. Microbiol. Immunol. 210, 211–219 (2021).
    pubmed: 34164720pmc: 8221277doi: 10.1007/s00430-021-00714-5google scholar: lookup
  74. Hsu SH et al. Peptidoglycan mediates Leptospira outer membrane protein Loa22 to toll-like receptor 2 for inflammatory interaction: a novel innate immune recognition. Sci. Rep. 11, 1064 (2021).
    pubmed: 33441663pmc: 8115183doi: 10.1038/s41598-020-79662-8google scholar: lookup
  75. Schuler EJA, Patel DT, Marconi RT. The leptospiral OmpA-like protein (Loa22) is a surface-exposed antigen that elicits bactericidal antibody against heterologous Leptospira. Vaccine X 15, 100382 (2023).
    pubmed: 37727366pmc: 10506094doi: 10.1016/j.jvacx.2023.100382google scholar: lookup
  76. Wang B, Sullivan JA, Sullivan GW, Mandell GL. Role of specific antibody in interaction of leptospires with human monocytes and monocyte-derived macrophages. Infect. Immun. 46, 809–813 (1984).
    pubmed: 6500713pmc: 261617doi: 10.1128/iai.46.3.809-813.1984google scholar: lookup
  77. Li S et al. Replication or death: distinct fates of pathogenic Leptospira strain Lai within macrophages of human or mouse origin. Innate Immun. 16, 80–92 (2010).
    pubmed: 19587003doi: 10.1177/1753425909105580google scholar: lookup
  78. Eshghi A et al. Leptospira interrogans catalase is required for resistance to H2O2 and for virulence. Infect. Immun. 80, 3892–3899 (2012).
    pubmed: 22927050pmc: 3486042doi: 10.1128/IAI.00466-12google scholar: lookup
  79. Fernando N et al. Protein carbonyl as a biomarker of oxidative stress in severe leptospirosis, and its usefulness in differentiating leptospirosis from dengue infections. PLoS ONE 11, e0156085 (2016).
    pubmed: 27280281pmc: 4900524doi: 10.1371/journal.pone.0156085google scholar: lookup
  80. Wang B, Sullivan J, Sullivan GW, Mandell GL. Interaction of leptospires with human polymorphonuclear neutrophils. Infect. Immun. 44, 459–464 (1984).
    pubmed: 6715045pmc: 263541doi: 10.1128/iai.44.2.459-464.1984google scholar: lookup
  81. Vieira ML et al. Leptospira interrogans outer membrane protein LipL21 is a potent inhibitor of neutrophil myeloperoxidase. Virulence 9, 414–425 (2018).
    pubmed: 29235397pmc: 5955187doi: 10.1080/21505594.2017.1407484google scholar: lookup
  82. Aratani Y. Myeloperoxidase: its role for host defense, inflammation, and neutrophil function. Arch. Biochem. Biophys. 640, 47–52 (2018).
    pubmed: 29336940doi: 10.1016/j.abb.2018.01.004google scholar: lookup
  83. Jost BH, Adler B, Vinh T, Faine S. A monoclonal antibody reacting with a determinant on leptospiral lipopolysaccharide protects guinea pigs against leptospirosis. J. Med. Microbiol. 22, 269–275 (1986).
    pubmed: 2430103doi: 10.1099/00222615-22-3-269google scholar: lookup
  84. Rees EM et al. Estimating the duration of antibody positivity and likely time of Leptospira infection using data from a cross-sectional serological study in Fiji. PLoS Negl. Trop. Dis. 16, e0010506 (2022).
    pubmed: 35696427pmc: 9232128doi: 10.1371/journal.pntd.0010506google scholar: lookup
  85. Grillová L et al. Circulating genotypes of Leptospira in French Polynesia: an 9-year molecular epidemiology surveillance follow-up study. PLoS Negl. Trop. Dis. 14, e0008662 (2020).
    pubmed: 32986693pmc: 7544043doi: 10.1371/journal.pntd.0008662google scholar: lookup
  86. Klimpel GR, Matthias MA, Vinetz JM. Leptospira interrogans activation of human peripheral blood mononuclear cells: preferential expansion of TCR gamma delta+ T cells vs TCR alpha beta+ T cells. J. Immunol. 171, 1447–1455 (2003).
    pubmed: 12874237doi: 10.4049/jimmunol.171.3.1447google scholar: lookup
  87. Krangvichian P et al. Impaired functions of human monocyte-derived dendritic cells and induction of regulatory T cells by pathogenic Leptospira. PLoS Negl. Trop. Dis. 17, e0011781 (2023).
    pubmed: 37983293pmc: 10695387doi: 10.1371/journal.pntd.0011781google scholar: lookup
  88. Sumaiya K, Natarajaseenivasan K. Macrophage migration inhibitory factor gene promoter polymorphism (−173G/C SNP) determines host susceptibility and severity of leptospirosis. Microb. Pathog. 164, 105445 (2022).
    pubmed: 35151822doi: 10.1016/j.micpath.2022.105445google scholar: lookup
  89. Esteves LM et al. Human leptospirosis: seroreactivity and genetic susceptibility in the population of São Miguel Island (Azores, Portugal). PLoS ONE 9, e108534 (2014).
    pubmed: 25255143pmc: 4177921doi: 10.1371/journal.pone.0108534google scholar: lookup
  90. Fialho RN et al. Role of human leukocyte antigen, killer-cell immunoglobulin-like receptors, and cytokine gene polymorphisms in leptospirosis. Hum. Immunol. 70, 915–920 (2009).
    pubmed: 19683555doi: 10.1016/j.humimm.2009.08.007google scholar: lookup
  91. Charon NW, Greenberg EP, Koopman MB, Limberger RJ. Spirochete chemotaxis, motility, and the structure of the spirochetal periplasmic flagella. Res. Microbiol. 143, 597–603 (1992).
    pubmed: 1475520doi: 10.1016/0923-2508(92)90117-7google scholar: lookup
  92. Vieira DS, Chaurasia R, Vinetz JM. Comparison of the PF07598-encoded virulence-modifying proteins of L. interrogans and L. borgpetersenii. Trop. Med. Infect. Dis. 8, 14 (2023).
    doi: 10.3390/tropicalmed8010014google scholar: lookup
  93. Chaurasia R, Vinetz JM. In silico prediction of molecular mechanisms of toxicity mediated by the leptospiral PF07598 gene family-encoded virulence-modifying proteins. Front. Mol. Biosci. 9, 1092197 (2022).
    pubmed: 36756251doi: 10.3389/fmolb.2022.1092197google scholar: lookup
  94. Safiee AW et al. Putative pathogenic genes of Leptospira interrogans and Leptospira weilii isolated from patients with acute febrile illness. Trop. Med. Infect. Dis. 7, 284 (2022).
    pubmed: 36288025pmc: 9610858doi: 10.3390/tropicalmed7100284google scholar: lookup
  95. Pinne M, Choy HA, Haake DA. The OmpL37 surface-exposed protein is expressed by pathogenic leptospira during infection and binds skin and vascular elastin. PLoS Negl. Trop. Dis. 4, e815 (2010).
    pubmed: 20844573pmc: 2935396doi: 10.1371/journal.pntd.0000815google scholar: lookup
  96. Barbosa AS, Isaac L. Strategies used by Leptospira spirochetes to evade the host complement system. FEBS Lett. 594, 2633–2644 (2020).
    pubmed: 32153015doi: 10.1002/1873-3468.13768google scholar: lookup
  97. Fraga TR, Barbosa AS, Isaac L. Leptospirosis: aspects of innate immunity, immunopathogenesis and immune evasion from the complement system. Scand. J. Immunol. 73, 408–419 (2011).
    pubmed: 21204903doi: 10.1111/j.1365-3083.2010.02505.xgoogle scholar: lookup
  98. Ren SX et al. Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing. Nature 422, 888–893 (2003).
    pubmed: 12712204doi: 10.1038/nature01597google scholar: lookup
  99. Carvalho E et al. Leptospiral TlyC is an extracellular matrix-binding protein and does not present hemolysin activity. FEBS Lett. 583, 1381–1385 (2009).
    pubmed: 19328790doi: 10.1016/j.febslet.2009.03.050google scholar: lookup
  100. Segers RP, van Gestel JA, van Eys GJ, van der Zeijst BA, Gaastra W. Presence of putative sphingomyelinase genes among members of the family Leptospiraceae. Infect. Immun. 60, 1707–1710 (1992).
    pubmed: 1548095pmc: 257053doi: 10.1128/iai.60.4.1707-1710.1992google scholar: lookup
  101. Narayanavari SA, Sritharan M, Haake DA, Matsunaga J. Multiple leptospiral sphingomyelinases (or are there?). Microbiology 158, 1137–1146 (2012).
    pubmed: 22422753pmc: 3542825doi: 10.1099/mic.0.057737-0google scholar: lookup
  102. Chacko CS et al. A short review on leptospirosis: clinical manifestations, diagnosis and treatment. Clin. Epidemiol. Glob. Health 11, 100741 (2021).
    doi: 10.1016/j.cegh.2021.100741google scholar: lookup
  103. Centers for Disease Control and Prevention. Leptospirosis. 2023.
  104. Ganoza CA et al. Asymptomatic renal colonization of humans in the peruvian Amazon by Leptospira. PLoS Negl. Trop. Dis. 4, e612 (2010).
    pubmed: 20186328pmc: 2826405doi: 10.1371/journal.pntd.0000612google scholar: lookup
  105. Ashford DA et al. Asymptomatic infection and risk factors for leptospirosis in Nicaragua. Am. J. Trop. Med. Hyg. 63, 249–254 (2000).
    pubmed: 11421372doi: 10.4269/ajtmh.2000.63.249google scholar: lookup
  106. Rajapakse S et al. Seroprevalence of leptospirosis in an endemic mixed urban and semi-urban setting — a community-based study in the district of Colombo, Sri Lanka. PLoS Negl. Trop. Dis. 14, e0008309 (2020).
    pubmed: 32428003pmc: 7263638doi: 10.1371/journal.pntd.0008309google scholar: lookup
  107. Almeida DS et al. Investigation of chronic infection by Leptospira spp. in asymptomatic sheep slaughtered in slaughterhouse. PLoS ONE 14, e0217391 (2019).
    pubmed: 31120961pmc: 6532964doi: 10.1371/journal.pone.0217391google scholar: lookup
  108. Boey K, Shiokawa K, Rajeev S. Leptospira infection in rats: a literature review of global prevalence and distribution. PLoS Negl. Trop. Dis. 13, e0007499 (2019).
    pubmed: 31398190pmc: 6688788doi: 10.1371/journal.pntd.0007499google scholar: lookup
  109. Sant’Anna da Costa R et al. Persistent high leptospiral shedding by asymptomatic dogs in endemic areas triggers a serious public health concern. Animals 2021.
    doi: 10.3390/ani11040937google scholar: lookup
  110. Ko AI, Goarant C, Picardeau M. Leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen. Nat. Rev. Microbiol. 7, 736–747 (2009).
    pubmed: 19756012pmc: 3384523doi: 10.1038/nrmicro2208google scholar: lookup
  111. Rajapakse S. Leptospirosis: clinical aspects. Clin. Med. 22, 14–17 (2022).
    doi: 10.7861/clinmed.2021-0784google scholar: lookup
  112. Araujo ER et al. Acute kidney injury in human leptospirosis: an immunohistochemical study with pathophysiological correlation. Virchows Arch. 456, 367–375 (2010).
    pubmed: 20217429doi: 10.1007/s00428-010-0894-8google scholar: lookup
  113. Yang CW. Leptospirosis renal disease: understanding the initiation by Toll-like receptors. Kidney Int. 72, 918–925 (2007).
    pubmed: 17687261doi: 10.1038/sj.ki.5002393google scholar: lookup
  114. Rajapakse S et al. Clinical and laboratory associations of severity in a Sri Lankan cohort of patients with serologically confirmed leptospirosis: a prospective study. Trans. R. Soc. Trop. Med. Hyg. 109, 710–716 (2015).
    pubmed: 26464233doi: 10.1093/trstmh/trv079google scholar: lookup
  115. Nicodemo AC, Duarte-Neto AN. Pathogenesis of pulmonary hemorrhagic syndrome in human leptospirosis. Am. J. Trop. Med. Hyg. 104, 1970–1972 (2021).
    pubmed: 33872210pmc: 8176490doi: 10.4269/ajtmh.20-1000google scholar: lookup
  116. Taylor AJ, Paris DH, Newton PN. A systematic review of the mortality from untreated leptospirosis. PLoS Negl. Trop. Dis. 9, e0003866 (2015).
    pubmed: 26110270pmc: 4482028doi: 10.1371/journal.pntd.0003866google scholar: lookup
  117. Rajapakse S, Rodrigo C, Haniffa R. Developing a clinically relevant classification to predict mortality in severe leptospirosis. J. Emerg. Trauma Shock. 3, 213–219 (2010).
    pubmed: 20930963pmc: 2938484doi: 10.4103/0974-2700.66519google scholar: lookup
  118. Bhatia M, Umapathy BL, Navaneeth BV. An evaluation of dark field microscopy, culture and commercial serological kits in the diagnosis of leptospirosis. Indian J. Med. Microbiol. 33, 416–421 (2015).
    pubmed: 26068347doi: 10.4103/0255-0857.158570google scholar: lookup
  119. Guedes IB et al. Leptospira transport medium (LTM): a practical tool for leptospires isolation. J. Microbiol. Methods 175, 105995 (2020).
    pubmed: 32593629doi: 10.1016/j.mimet.2020.105995google scholar: lookup
  120. Goarant C, Girault D, Thibeaux R, Soupé-Gilbert ME. Isolation and culture of leptospira from clinical and environmental samples. Methods Mol. Biol. 2134, 1–9 (2020).
    pubmed: 32632854doi: 10.1007/978-1-0716-0459-5_1google scholar: lookup
  121. Goris MG, Hartskeerl RA. Leptospirosis serodiagnosis by the microscopic agglutination test. Curr. Protoc. Microbiol. 32, 12E.15 (2014).
    doi: 10.1002/9780471729259.mc12e05s32google scholar: lookup
  122. Guernier V, Goarant C, Benschop J, Lau CL. A systematic review of human and animal leptospirosis in the Pacific Islands reveals pathogen and reservoir diversity. PLoS Negl. Trop. Dis. 12, e0006503 (2018).
    pubmed: 29758037pmc: 5967813doi: 10.1371/journal.pntd.0006503google scholar: lookup
  123. Signorini ML, Lottersberger J, Tarabla HD, Vanasco NB. Enzyme-linked immunosorbent assay to diagnose human leptospirosis: a meta-analysis of the published literature. Epidemiol. Infect. 141, 22–32 (2013).
    pubmed: 22953720doi: 10.1017/S0950268812001951google scholar: lookup
  124. Rosa MI et al. IgM ELISA for leptospirosis diagnosis: a systematic review and meta-analysis. Cien. Saude Colet. 22, 4001–4012 (2017).
    pubmed: 29267717doi: 10.1590/1413-812320172212.14112016google scholar: lookup
  125. Sreevalsan TV, Chandra R. Relevance of polymerase chain reaction in early diagnosis of leptospirosis. Indian J. Crit. Care Med. 28, 290–293 (2024).
    pubmed: 38477003pmc: 10926039doi: 10.5005/jp-journals-10071-24649google scholar: lookup
  126. Croda J et al. Leptospira immunoglobulin-like proteins as a serodiagnostic marker for acute leptospirosis. J. Clin. Microbiol. 45, 1528–1534 (2007).
    pubmed: 17360842pmc: 1865864doi: 10.1128/JCM.02344-06google scholar: lookup
  127. Picardeau M. Diagnosis and epidemiology of leptospirosis. Med. Mal. Infect. 43, 1–9 (2013).
    pubmed: 23337900doi: 10.1016/j.medmal.2012.11.005google scholar: lookup
  128. Levett PN. Usefulness of serologic analysis as a predictor of the infecting serovar in patients with severe leptospirosis. Clin. Infect. Dis. 36, 447–452 (2003).
    pubmed: 12567302doi: 10.1086/346208google scholar: lookup
  129. Eugene EJ et al. Evaluation of two immunodiagnostic tests for early rapid diagnosis of leptospirosis in Sri Lanka: a preliminary study. BMC Infect. Dis. 15, 319 (2015).
    pubmed: 26259957pmc: 4531393doi: 10.1186/s12879-015-1080-zgoogle scholar: lookup
  130. Goris MG et al. Prospective evaluation of three rapid diagnostic tests for diagnosis of human leptospirosis. PLoS Negl. Trop. Dis. 7, e2290 (2013).
    pubmed: 23875034pmc: 3708816doi: 10.1371/journal.pntd.0002290google scholar: lookup
  131. Behera SK et al. Diagnosis of human leptospirosis: comparison of microscopic agglutination test with recombinant LigA/B antigen-based in-house IgM dot ELISA dipstick test and latex agglutination test using bayesian latent class model and MAT as gold standard. Diagnostics 12, 1455 (2022).
    pubmed: 35741265pmc: 9221883doi: 10.3390/diagnostics12061455google scholar: lookup
  132. Suwancharoen D, Sittiwicheanwong B, Wiratsudakul A. Evaluation of loop-mediated isothermal amplification method (LAMP) for pathogenic Leptospira spp. detection with leptospires isolation and real-time PCR. J. Vet. Med. Sci. 78, 1299–1302 (2016).
    pubmed: 27150208pmc: 5053931doi: 10.1292/jvms.15-0702google scholar: lookup
  133. Podgoršek D et al. Evaluation of real-time PCR targeting the lipL32 gene for diagnosis of Leptospira infection. BMC Microbiol. 20, 59 (2020).
    pubmed: 32160864pmc: 7066766doi: 10.1186/s12866-020-01744-4google scholar: lookup
  134. Castro-Wallace SL et al. Nanopore DNA sequencing and genome assembly on the international space station. Sci. Rep. 7, 18022 (2017).
    pubmed: 29269933pmc: 5740133doi: 10.1038/s41598-017-18364-0google scholar: lookup
  135. Chiu CY, Miller SA. Clinical metagenomics. Nat. Rev. Genet. 20, 341–355 (2019).
    pubmed: 30918369pmc: 6858796doi: 10.1038/s41576-019-0113-7google scholar: lookup
  136. Allicock OM et al. BacCapSeq: a platform for diagnosis and characterization of bacterial infections. mBio 2018.
    doi: 10.1128/mbio.02007-18google scholar: lookup
  137. Rajapakse S et al. A diagnostic scoring model for leptospirosis in resource limited settings. PLoS Negl. Trop. Dis. 10, e0004513 (2016).
    pubmed: 27333195pmc: 4917116doi: 10.1371/journal.pntd.0004513google scholar: lookup
  138. Sigera PC et al. Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study. BMC Infect. Dis. 19, 680 (2019).
    pubmed: 31370795pmc: 6676631doi: 10.1186/s12879-019-4304-9google scholar: lookup
  139. Lau CL, DePasquale JM. Leptospirosis, diagnostic challenges, American Samoa. Emerg. Infect. Dis. 18, 2079–2081 (2012).
    pubmed: 23171761pmc: 3557872doi: 10.3201/eid1812.120429google scholar: lookup
  140. De Silva NL et al. Changes in full blood count parameters in leptospirosis: a prospective study. Int. Arch. Med. 7, 31 (2014).
    pubmed: 25018781pmc: 4094533doi: 10.1186/1755-7682-7-31google scholar: lookup
  141. de Silva NL et al. Can findings on peripheral blood smear differentiate leptospirosis from other infections? A preliminary comparative study. Trans. R. Soc. Trop. Med. Hyg. 112, 94–96 (2018).
    pubmed: 29617885doi: 10.1093/trstmh/try024google scholar: lookup
  142. Sukmark T et al. Thai-Lepto-on-admission probability (THAI-LEPTO) score as an early tool for initial diagnosis of leptospirosis: result from Thai-Lepto AKI study group. PLoS Negl. Trop. Dis. 12, e0006319 (2018).
    pubmed: 29554124pmc: 5875898doi: 10.1371/journal.pntd.0006319google scholar: lookup
  143. Temeiam N, Jareinpituk S, Phinyo P, Patumanond J, Srisawat N. Development and validation of a simple score for diagnosis of Leptospirosis at outpatient departments. PLoS Negl. Trop. Dis. 14, e0007977 (2020).
    pubmed: 31917796pmc: 6975559doi: 10.1371/journal.pntd.0007977google scholar: lookup
  144. Al Hariri YK, Sulaiman SAS, Khan AH, Adnan AS, Al Ebrahem SQ. Mortality of leptospirosis associated acute kidney injury (LAKI) & predictors for its development in adults: a systematic review. J. Infect. public. health 12, 751–759 (2019).
    pubmed: 31281106doi: 10.1016/j.jiph.2019.06.014google scholar: lookup
  145. Smith S et al. A simple score to predict severe leptospirosis. PLoS Negl. Trop. Dis. 13, e0007205 (2019).
    pubmed: 30759081pmc: 6391019doi: 10.1371/journal.pntd.0007205google scholar: lookup
  146. Galdino GS et al. Development and validation of a simple machine learning tool to predict mortality in leptospirosis. Sci. Rep. 13, 4506 (2023).
    pubmed: 36934135pmc: 10024714doi: 10.1038/s41598-023-31707-4google scholar: lookup
  147. Marotto PC et al. Early identification of leptospirosis-associated pulmonary hemorrhage syndrome by use of a validated prediction model. J. Infect. 60, 218–223 (2010).
    pubmed: 20026189doi: 10.1016/j.jinf.2009.12.005google scholar: lookup
  148. Pongpan S, Thanatrakolsri P, Vittaporn S, Khamnuan P, Daraswang P. Prognostic factors for leptospirosis infection severity. Trop. Med. Infect. Dis. 2023.
    doi: 10.3390/tropicalmed8020112google scholar: lookup
  149. So RAY et al. A scoring tool to predict pulmonary complications in severe leptospirosis with kidney failure. Trop. Med. Infect. Dis. 2022.
    doi: 10.3390/tropicalmed7010007google scholar: lookup
  150. Ajjimarungsi A, Bhurayanontachai R, Chusri S. Clinical characteristics, outcomes, and predictors of leptospirosis in patients admitted to the medical intensive care unit: a retrospective analysis. J. Infect. Public Health 13, 2055–2061 (2020).
    pubmed: 33139235doi: 10.1016/j.jiph.2020.10.004google scholar: lookup
  151. Guernier V, Allan KJ, Goarant C. Advances and challenges in barcoding pathogenic and environmental Leptospira. Parasitology 145, 595–607 (2018).
    pubmed: 28716157doi: 10.1017/S0031182017001147google scholar: lookup
  152. Goarant C. Leptospirosis: risk factors and management challenges in developing countries. Res. Rep. Trop. Med. 7, 49–62 (2016).
    pubmed: 30050339pmc: 6028063
  153. World Health Organization. Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control. 2003.
  154. Hancock GA, Wilks CR, Kotiw M, Allen JD. The long term efficacy of a hardjo-pomona vaccine in preventing leptospiruria in cattle exposed to natural challenge with Leptospira interrogans serovar hardjo. Aust. Vet. J. 61, 54–56 (1984).
    pubmed: 6732669doi: 10.1111/j.1751-0813.1984.tb07192.xgoogle scholar: lookup
  155. Rinehart CL, Zimmerman AD, Buterbaugh RE, Jolie RA, Chase CC. Efficacy of vaccination of cattle with the Leptospira interrogans serovar hardjo type hardjoprajitno component of a pentavalent Leptospira bacterin against experimental challenge with Leptospira borgpetersenii serovar hardjo type hardjo-bovis. Am. J. Vet. Res. 73, 735–740 (2012).
    pubmed: 22533408doi: 10.2460/ajvr.73.5.735google scholar: lookup
  156. Nisa S et al. Diverse epidemiology of leptospira serovars notified in New Zealand, 1999–2017. Pathogens 2020.
    doi: 10.3390/pathogens9100841google scholar: lookup
  157. Win TZ et al. Antibiotic prophylaxis for leptospirosis. Cochrane Database Syst. Rev. 2024.
    doi: 10.1002/14651858.cd014959.pub2google scholar: lookup
  158. Alikhani A et al. Comparison of azithromycin vs doxycycline prophylaxis in leptospirosis, a randomized double blind placebo-controlled trial. J. Infect. Dev. Ctries 12, 991–995 (2018).
    pubmed: 32012129doi: 10.3855/jidc.10126google scholar: lookup
  159. Gonsalez CR et al. Use of doxycycline for leptospirosis after high-risk exposure in São Paulo, Brazil. Rev. Inst. Med. Trop. Sao Paulo 40, 59–61 (1998).
    pubmed: 9713140doi: 10.1590/S0036-46651998000100012google scholar: lookup
  160. Illangasekera VL, Kularatne SA, Kumarasiri PV, Pussepitiya D, Premaratne MD. Is oral penicillin an effective chemoprophylaxis against leptospirosis? A placebo controlled field study in the Kandy District, Sri Lanka. Southeast. Asian J. Trop. Med. Public Health 39, 882–884 (2008).
    pubmed: 19058584
  161. Sehgal SC, Sugunan AP, Murhekar MV, Sharma S, Vijayachari P. Randomized controlled trial of doxycycline prophylaxis against leptospirosis in an endemic area. Int. J. Antimicrob. Agents 13, 249–255 (2000).
    pubmed: 10755239doi: 10.1016/S0924-8579(99)00134-Xgoogle scholar: lookup
  162. Takafuji ET et al. An efficacy trial of doxycycline chemoprophylaxis against leptospirosis. N. Engl. J. Med. 310, 497–500 (1984).
    pubmed: 6363930doi: 10.1056/NEJM198402233100805google scholar: lookup
  163. Brett-Major DM, Lipnick RJ. Antibiotic prophylaxis for leptospirosis. Cochrane Database Syst. Rev. 2009.
    doi: 10.1002/14651858.cd007342.pub2google scholar: lookup
  164. Yanagihara Y, Villanueva SY, Yoshida S, Okamoto Y, Masuzawa T. Current status of leptospirosis in Japan and Philippines. Comp. Immunol. Microbiol. Infect. Dis. 30, 399–413 (2007).
    pubmed: 17614131doi: 10.1016/j.cimid.2007.05.003google scholar: lookup
  165. Martínez R et al. Efficacy and safety of a vaccine against human leptospirosis in Cuba. Rev. Panam. Salud Publica 15, 249–255 (2004).
    pubmed: 15193180
  166. Laurichesse H et al. Safety and immunogenicity of subcutaneous or intramuscular administration of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae in healthy volunteers. Clin. Microbiol. Infect. 13, 395–403 (2007).
    pubmed: 17359323doi: 10.1111/j.1469-0691.2007.01662.xgoogle scholar: lookup
  167. Yan Y et al. An evaluation of the serological and epidemiological effects of the outer envelope vaccine to leptospira. J. Chin. Med. Assoc. 66, 224–230 (2003).
    pubmed: 12854874
  168. Koizumi N, Watanabe H. Leptospirosis vaccines: past, present, and future. J. Postgrad. Med. 51, 210–214 (2005).
    pubmed: 16333195
  169. Wunder EA et al. A live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus. eLife 10, e64166 (2021).
    pubmed: 33496263pmc: 7837694doi: 10.7554/eLife.64166google scholar: lookup
  170. Silveira MM et al. DNA vaccines against leptospirosis: a literature review. Vaccine 35, 5559–5567 (2017).
    pubmed: 28882437doi: 10.1016/j.vaccine.2017.08.067google scholar: lookup
  171. Barazzone GC et al. Revisiting the development of vaccines against pathogenic leptospira: innovative approaches, present challenges, and future perspectives. Front. Immunol. 12, 760291 (2021).
    pubmed: 35046936doi: 10.3389/fimmu.2021.760291google scholar: lookup
  172. Lin MH et al. LipL41, a hemin binding protein from Leptospira santarosai serovar Shermani. PLoS ONE 8, e83246 (2013).
    pubmed: 24349474pmc: 3861479doi: 10.1371/journal.pone.0083246google scholar: lookup
  173. Dellagostin OA et al. Recombinant vaccines against leptospirosis. Hum. Vaccin. 7, 1215–1224 (2011).
    pubmed: 22048111doi: 10.4161/hv.7.11.17944google scholar: lookup
  174. Haake DA et al. Characterization of leptospiral outer membrane lipoprotein LipL36: downregulation associated with late-log-phase growth and mammalian infection. Infect. Immun. 66, 1579–1587 (1998).
    pubmed: 9529084pmc: 108091doi: 10.1128/IAI.66.4.1579-1587.1998google scholar: lookup
  175. Vijayachari P et al. Immunogenicity of a novel enhanced consensus DNA vaccine encoding the leptospiral protein LipL45. Hum. Vaccin. Immunother. 11, 1945–1953 (2015).
    pubmed: 26020621pmc: 4635901doi: 10.1080/21645515.2015.1047117google scholar: lookup
  176. Buaklin A et al. Optimization of the immunogenicity of a DNA vaccine encoding a bacterial outer membrane lipoprotein. Mol. Biotechnol. 56, 903–910 (2014).
    pubmed: 24870617doi: 10.1007/s12033-014-9769-6google scholar: lookup
  177. Faisal SM et al. Evaluation of protective immunity of Leptospira immunoglobulin like protein A (LigA) DNA vaccine against challenge in hamsters. Vaccine 26, 277–287 (2008).
    pubmed: 18055070doi: 10.1016/j.vaccine.2007.10.029google scholar: lookup
  178. Feng CY et al. Immune strategies using single-component LipL32 and multi-component recombinant LipL32-41-OmpL1 vaccines against leptospira. Braz. J. Med. Biol. Res. 42, 796–803 (2009).
    pubmed: 19649391doi: 10.1590/S0100-879X2009005000013google scholar: lookup
  179. Umthong S et al. Immunogenicity of a DNA and recombinant protein vaccine combining LipL32 and Loa22 for leptospirosis using chitosan as a delivery system. J. Microbiol. Biotechnol. 25, 526–536 (2015).
    pubmed: 25348693doi: 10.4014/jmb.1408.08007google scholar: lookup
  180. Kumar P, Lata S, Shankar UN, Akif M. Immunoinformatics-based designing of a multi-epitope chimeric vaccine from multi-domain outer surface antigens of leptospira. Front. Immunol. 2021.
    doi: 10.3389/fimmu.2021.735373google scholar: lookup
  181. Validi M, Karkhah A, Prajapati VK, Nouri HR. Immuno-informatics based approaches to design a novel multi epitope-based vaccine for immune response reinforcement against Leptospirosis. Mol. Immunol. 104, 128–138 (2018).
    pubmed: 30448609doi: 10.1016/j.molimm.2018.11.005google scholar: lookup
  182. Techawiwattanaboon T et al. Designing adjuvant formulations to promote immunogenicity and protective efficacy of leptospira immunoglobulin-like protein a subunit vaccine. Front. Cell. Infect. Microbiol. 2022.
    doi: 10.3389/fcimb.2022.918629google scholar: lookup
  183. Varma VP, Kadivella M, Kumar A, Kavela S, Faisal SM. LigA formulated in AS04 or montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis. Front. Immunol. 2022.
    doi: 10.3389/fimmu.2022.985802google scholar: lookup
  184. Yang HL et al. In silico and microarray-based genomic approaches to identifying potential vaccine candidates against Leptospira interrogans. BMC Genomics 2006.
    doi: 10.1186/1471-2164-7-293google scholar: lookup
  185. Techawiwattanaboon T et al. Proteomic profile of naturally released extracellular vesicles secreted from leptospira interrogans serovar pomona in response to temperature and osmotic stresses. Sci. Rep. 2023.
    doi: 10.1038/s41598-023-45863-0google scholar: lookup
  186. Trott DJ, Abraham S, Adler B. Antimicrobial resistance in Leptospira, Brucella, and other rarely investigated veterinary and zoonotic pathogens. Microbiol. Spectr. 2018.
    doi: 10.1128/microbiolspec.arba-0029-2017google scholar: lookup
  187. Charan J, Saxena D, Mulla S, Yadav P. Antibiotics for the treatment of leptospirosis: systematic review and meta-analysis of controlled trials. Int. J. Prev. Med. 4, 501–510 (2013).
    pubmed: 23930159pmc: 3733179
  188. Suputtamongkol Y et al. An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin. Infect. Dis. 39, 1417–1424 (2004).
    pubmed: 15546074doi: 10.1086/425001google scholar: lookup
  189. Selvarajah S, Ran S, Roberts NW, Nair M. Leptospirosis in pregnancy: a systematic review. PLoS Negl. Trop. Dis. 15, e0009747 (2021).
    pubmed: 34520461pmc: 8462732doi: 10.1371/journal.pntd.0009747google scholar: lookup
  190. Win TZ et al. Antibiotics for treatment of leptospirosis. Cochrane Database Syst. Rev. 2024.
    doi: 10.1002/14651858.cd014960.pub2google scholar: lookup
  191. Fernando N et al. Effect of antimicrobial agents on inflammatory cytokines in acute leptospirosis. Antimicrob. Agents Chemother. 2018.
    doi: 10.1128/aac.02312-17google scholar: lookup
  192. Zhang W et al. Doxycycline attenuates leptospira-induced IL-1β by suppressing nlrp3 inflammasome priming. Front. Immunol. 8, 857 (2017).
    pubmed: 28791016pmc: 5522854doi: 10.3389/fimmu.2017.00857google scholar: lookup
  193. Guerrier G, D’Ortenzio E. The Jarisch–Herxheimer reaction in leptospirosis: a systematic review. PLoS ONE 8, e59266 (2013).
    pubmed: 23555644pmc: 3608636doi: 10.1371/journal.pone.0059266google scholar: lookup
  194. Takamizawa S et al. Leptospirosis and Jarisch–Herxheimer reaction. QJM 108, 967–968 (2015).
    pubmed: 25862773doi: 10.1093/qjmed/hcv077google scholar: lookup
  195. Guerrier G, Lefèvre P, Chouvin C, D’Ortenzio E. Jarisch–Herxheimer reaction among patients with leptospirosis: incidence and risk factors. Am. J. Trop. Med. Hyg. 96, 791–794 (2017).
    pubmed: 28115662pmc: 5392622doi: 10.4269/ajtmh.16-0457google scholar: lookup
  196. Smith S et al. Severe leptospirosis in tropical Australia: optimising intensive care unit management to reduce mortality. PLoS Negl. Trop. Dis. 13, e0007929 (2019).
    pubmed: 31790405pmc: 6907868doi: 10.1371/journal.pntd.0007929google scholar: lookup
  197. Rodrigo C et al. High dose corticosteroids in severe leptospirosis: a systematic review. Trans. R. Soc. Trop. Med. Hyg. 108, 743–750 (2014).
    pubmed: 25266477doi: 10.1093/trstmh/tru148google scholar: lookup
  198. Davoodi L et al. Evaluation of the effectiveness of N-acetylcysteine on accelerating the recovery of renal failure in patients with leptospirosis, a randomized clinical trial study. Ann. Med. Surg. 67, 102518 (2021).
    doi: 10.1016/j.amsu.2021.102518google scholar: lookup
  199. Herath N et al. Sequel and therapeutic modalities of leptospirosis associated severe pulmonary haemorrhagic syndrome (SPHS); a Sri Lankan experience. BMC Infect. Dis. 19, 451 (2019).
    pubmed: 31113404pmc: 6530063doi: 10.1186/s12879-019-4094-0google scholar: lookup
  200. Trivedi SV et al. Plasma exchange with immunosuppression in pulmonary alveolar haemorrhage due to leptospirosis. Indian J. Med. Res. 131, 429–433 (2010).
    pubmed: 20418558
  201. Fonseka CL, Lekamwasam S. Role of plasmapheresis and extracorporeal membrane oxygenation in the treatment of leptospirosis complicated with pulmonary hemorrhages. J. Trop. Med. 2018, 4520185 (2018).
    pubmed: 30631369pmc: 6304550doi: 10.1155/2018/4520185google scholar: lookup
  202. Biggs HM et al. Leptospirosis among hospitalized febrile patients in Northern Tanzania. Am. J. Trop. Med. Hyg. 85, 275–281 (2011).
    pubmed: 21813847pmc: 3144825doi: 10.4269/ajtmh.2011.11-0176google scholar: lookup
  203. Ismail TF et al. Retrospective serosurvey of leptospirosis among patients with acute febrile illness and hepatitis in Egypt. Am. J. Trop. Med. Hyg. 75, 1085–1089 (2006).
    pubmed: 17172371doi: 10.4269/ajtmh.2006.75.1085google scholar: lookup
  204. Crump JA et al. Etiology of severe non-malaria febrile illness in Northern Tanzania: a prospective cohort study. PLoS Negl. Trop. Dis. 7, e2324 (2013).
    pubmed: 23875053pmc: 3715424doi: 10.1371/journal.pntd.0002324google scholar: lookup
  205. Torgerson PR et al. Global burden of leptospirosis: estimated in terms of disability adjusted life years. PLoS Negl. Trop. Dis. 9, e0004122 (2015).
    pubmed: 26431366pmc: 4591975doi: 10.1371/journal.pntd.0004122google scholar: lookup
  206. Ellis WA. in Leptospira and Leptospirosis. 2015.
  207. Engida HA, Theuri DM, Gathungu DK, Gachohi J. Optimal control and cost-effectiveness analysis for leptospirosis epidemic. J. Biol. Dyn. 17, 2248178 (2023).
    pubmed: 37695860doi: 10.1080/17513758.2023.2248178google scholar: lookup
  208. Sanhueza JM et al. Estimation of the burden of leptospirosis in New Zealand. Zoonoses Public Health 67, 167–176 (2020).
    pubmed: 31799801doi: 10.1111/zph.12668google scholar: lookup
  209. Galloway RL, Levett PN, Tumeh JW, Flowers CR. Assessing cost effectiveness of empirical and prophylactic therapy for managing leptospirosis outbreaks. Epidemiol. Infect. 137, 1323–1332 (2009).
    pubmed: 19161641doi: 10.1017/S0950268808001751google scholar: lookup
  210. Agampodi S, Gunarathna S, Lee JS, Excler JL. Global, regional, and country-level cost of leptospirosis due to loss of productivity in humans. PLoS Negl. Trop. Dis. 17, e0011291 (2023).
    pubmed: 37616329pmc: 10482283doi: 10.1371/journal.pntd.0011291google scholar: lookup
  211. Goris MG et al. Towards the burden of human leptospirosis: duration of acute illness and occurrence of post-leptospirosis symptoms of patients in the Netherlands. PLoS ONE 8, e76549 (2013).
    pubmed: 24098528pmc: 3789694doi: 10.1371/journal.pone.0076549google scholar: lookup
  212. Cvejic E et al. Contribution of individual psychological and psychosocial factors to symptom severity and time-to-recovery after naturally-occurring acute infective illness: the Dubbo Infection Outcomes Study (DIOS). Brain Behav. Immun. 82, 76–83 (2019).
    pubmed: 31376496doi: 10.1016/j.bbi.2019.07.034google scholar: lookup
  213. Chang CH et al. Long-term outcome of leptospirosis infection with acute kidney injury. Biomedicines 2022.
    doi: 10.3390/biomedicines10102338google scholar: lookup
  214. Phannajit J et al. Long-term kidney outcomes after leptospirosis: a prospective multicentre cohort study in Thailand. Nephrol. Dial. Transpl. 38, 2182–2191 (2023).
    doi: 10.1093/ndt/gfad030google scholar: lookup
  215. Premarathne SS et al. Leptospirosis: a potential culprit for chronic kidney disease of uncertain etiology. Nephron 147, 510–520 (2023).
    pubmed: 36809758doi: 10.1159/000528703google scholar: lookup
  216. Carrillo-Larco RM, Altez-Fernandez C, Acevedo-Rodriguez JG, Ortiz-Acha K, Ugarte-Gil C. Leptospirosis as a risk factor for chronic kidney disease: a systematic review of observational studies. PLoS Negl. Trop. Dis. 13, e0007458 (2019).
    pubmed: 31120876pmc: 6550415doi: 10.1371/journal.pntd.0007458google scholar: lookup
  217. Prado LG, Barbosa AS. Understanding the renal fibrotic process in leptospirosis. Int. J. Mol. Sci. 2021.
    doi: 10.3390/ijms221910779google scholar: lookup
  218. Hotez PJ, Aksoy S, Brindley PJ, Kamhawi S. What constitutes a neglected tropical disease?. PLoS Negl. Trop. Dis. 14, e0008001 (2020).
    pubmed: 31999732pmc: 6991948doi: 10.1371/journal.pntd.0008001google scholar: lookup
  219. Hotez PJ, Woc-Colburn L, Bottazzi ME. Neglected tropical diseases in Central America and Panama: review of their prevalence, populations at risk and impact on regional development. Int. J. Parasitol. 44, 597–603 (2014).
    pubmed: 24846528doi: 10.1016/j.ijpara.2014.04.001google scholar: lookup
  220. Karpagam KB, Ganesh B. Leptospirosis: a neglected tropical zoonotic infection of public health importance — an updated review. Eur. J. Clin. Microbiol. Infect. Dis. 39, 835–846 (2020).
    pubmed: 31898795doi: 10.1007/s10096-019-03797-4google scholar: lookup
  221. Costa E et al. Penicillin at the late stage of leptospirosis: a randomized controlled trial. Rev. Inst. Med. Trop. Sao Paulo 45, 141–145 (2003).
    pubmed: 12870063doi: 10.1590/S0036-46652003000300005google scholar: lookup
  222. Daher EF, Nogueira CB. Evaluation of penicillin therapy in patients with leptospirosis and acute renal failure. Rev. Inst. Med. Trop. Sao Paulo 42, 327–332 (2000).
    pubmed: 11136519doi: 10.1590/S0036-46652000000600005google scholar: lookup
  223. Edwards CN, Nicholson GD, Hassell TA, Everard CO, Callender J. Penicillin therapy in icteric leptospirosis. Am. J. Trop. Med. Hyg. 39, 388–390 (1988).
    pubmed: 3189700doi: 10.4269/ajtmh.1988.39.388google scholar: lookup
  224. Fairburn AC, Semple SJ. Chloramphenicol and penicillin in the treatment of leptospirosis among British troops in Malaya. Lancet 270, 13–16 (1956).
    pubmed: 13279151doi: 10.1016/S0140-6736(56)91853-0google scholar: lookup
  225. McClain JB, Ballou WR, Harrison SM, Steinweg DL. Doxycycline therapy for leptospirosis. Ann. Intern. Med. 100, 696–698 (1984).
    pubmed: 6712032doi: 10.7326/0003-4819-100-5-696google scholar: lookup
  226. Panaphut T, Domrongkitchaiporn S, Vibhagool A, Thinkamrop B, Susaengrat W. Ceftriaxone compared with sodium penicillin g for treatment of severe leptospirosis. Clin. Infect. Dis. 36, 1507–1513 (2003).
    pubmed: 12802748doi: 10.1086/375226google scholar: lookup
  227. Phimda K et al. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob. Agents Chemother. 51, 3259–3263 (2007).
    pubmed: 17638700pmc: 2043199doi: 10.1128/AAC.00508-07google scholar: lookup
  228. Watt G et al. Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis. Lancet 1, 433–435 (1988).
    pubmed: 2893865doi: 10.1016/S0140-6736(88)91230-5google scholar: lookup
  229. Russell RW. Treatment of leptospirosis with oxytetracycline. Lancet 2, 1143–1145 (1958).
    pubmed: 13612142doi: 10.1016/S0140-6736(58)92405-Xgoogle scholar: lookup
  230. Rajapakse S, Rodrigo C, Balaji K, Fernando SD. Atypical manifestations of leptospirosis. Trans. R. Soc. Trop. Med. Hyg. 109, 294–302 (2015).
    pubmed: 25813883doi: 10.1093/trstmh/trv026google scholar: lookup
  231. Vilaichone RK, Mahachai V, Wilde H. Acute acalculous cholecystitis in leptospirosis. J. Clin. Gastroenterol. 29, 280–283 (1999).
    pubmed: 10509958doi: 10.1097/00004836-199910000-00012google scholar: lookup
  232. Ranawaka N, Jeevagan V, Karunanayake P, Jayasinghe S. Pancreatitis and myocarditis followed by pulmonary hemorrhage, a rare presentation of leptospirosis — a case report and literature survey. BMC Infect. Dis. 13, 38 (2013).
    pubmed: 23347428pmc: 3560203doi: 10.1186/1471-2334-13-38google scholar: lookup
  233. Solmazgul E et al. A case of Weil’s syndrome developing steroid resistant immune haemolytic anaemia. Scand. J. Infect. Dis. 37, 700–702 (2005).
    pubmed: 16126576doi: 10.1080/00365540510040214google scholar: lookup
  234. Hanvanich M, Moollaor P, Suwangool P, Sitprija V. Hemolytic uremic syndrome in leptospirosis bataviae. Nephron 40, 230–231 (1985).
    pubmed: 4000352doi: 10.1159/000183465google scholar: lookup
  235. Laing RW, Teh C, Toh CH. Thrombotic thrombocytopenic purpura (TTP) complicating leptospirosis: a previously undescribed association. J. Clin. Pathol. 43, 961–962 (1990).
    pubmed: 2262572pmc: 502915doi: 10.1136/jcp.43.11.961-cgoogle scholar: lookup
  236. Panicker JN, Mammachan R, Jayakumar RV. Primary neuroleptospirosis. Postgrad. Med. J. 77, 589–590 (2001).
    pubmed: 11524519pmc: 1757912doi: 10.1136/pmj.77.911.589google scholar: lookup
  237. Chandra SR et al. Acute disseminated encephalomyelitis following leptospirosis. J. Assoc. Physicians India 52, 327–329 (2004).
    pubmed: 15636341
  238. Sakellaridis N, Panagopoulos D, Androulis A. Neuroleptospirosis with hydrocephalus and very elevated cerebrospinal fluid protein. South. Med. J. 102, 549–550 (2009).
    pubmed: 19373140doi: 10.1097/SMJ.0b013e3181a0ae80google scholar: lookup
  239. Dimopoulou I et al. Leptospirosis presenting with encephalitis-induced coma. Intensive Care Med. 28, 1682 (2002).
    pubmed: 12585240doi: 10.1007/s00134-002-1476-2google scholar: lookup
  240. Kavitha S, Shastry BA. Leptospirosis with transverse myelitis. J. Assoc. Physicians India 53, 159–160 (2005).
    pubmed: 15847045
  241. Bal AM, Bharadwaj RS, Gita N, Joshi SA, Thakare JP. Guillain–Barre syndrome in a pediatric patient following infection due to Leptospira. Jpn J. Infect. Dis. 56, 29–31 (2003).
    pubmed: 12711824doi: 10.7883/yoken.JJID.2003.29google scholar: lookup
  242. Hancox RJ, Karalus N, Singh V. Mononeuritis multiplex in leptospirosis. Scand. J. Infect. Dis. 23, 395–396 (1991).
    pubmed: 1882206doi: 10.3109/00365549109024332google scholar: lookup
  243. Turhan V et al. Cerebral venous thrombosis as a complication of leptospirosis. J. Infect. 53, e247–e249 (2006).
    pubmed: 16603251doi: 10.1016/j.jinf.2006.02.013google scholar: lookup
  244. Chu KM, Rathinam R, Namperumalsamy P, Dean D. Identification of Leptospira species in the pathogenesis of uveitis and determination of clinical ocular characteristics in south India. J. Infect. Dis. 177, 1314–1321 (1998).
    pubmed: 9593018doi: 10.1086/515273google scholar: lookup
  245. Levin N et al. Panuveitis with papillitis in leptospirosis. Am. J. Ophthalmol. 117, 118–119 (1994).
    pubmed: 8291582doi: 10.1016/S0002-9394(14)73030-2google scholar: lookup
  246. Faine S, Adler B, Christopher W, Valentine R. Fatal congenital human leptospirosis. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 257, 548 (1984).
    pubmed: 6542285
  247. Sharma KK, Madhvilatha P, Kalawat U, Sivakumar V. Leptospirosis-induced still birth and postpartum sepsis. Indian J. Pathol. Microbiol. 54, 426–427 (2011).
    pubmed: 21623124doi: 10.4103/0377-4929.81617google scholar: lookup
  248. Shaked Y, Shpilberg O, Samra D, Samra Y. Leptospirosis in pregnancy and its effect on the fetus: case report and review. Clin. Infect. Dis. 17, 241–243 (1993).
    pubmed: 8399874doi: 10.1093/clinids/17.2.241google scholar: lookup
  249. Tramoni G, Clément HJ, Lopez F, Viale JP. An unusual case of post partum haemorrhage: leptospirosis infection [French]. Ann. Fr. Anesth. Reanim. 22, 363–365 (2003).
    pubmed: 12818331doi: 10.1016/S0750-7658(03)00061-3google scholar: lookup

Citations

This article has been cited 11 times.
  1. Ristiyanto R, Handayani FD, Kartika W, Mulyono A, Widoretno W, Maha MS, Lienggonegoro LA, Pangaribuan HU, Suryaningtyas NH, Gasem MH. Application of leptospirosis surveillance study at primary health care center in Banyumas and Demak, Central Java, Indonesia. Open Vet J 2025 Nov;15(11):5961-5970.
    doi: 10.5455/OVJ.2025.v15.i11.51pubmed: 41630749google scholar: lookup
  2. Ruwanpathirana P, Rambukwella R, Perera N, Priyankara D. Severe leptospirosis in the intensive care unit: single centre prospective cohort study from Sri Lanka. BMC Infect Dis 2026 Jan 8;26(1):265.
    doi: 10.1186/s12879-025-12477-ypubmed: 41507816google scholar: lookup
  3. Bonilla-Sánchez CA, Rivera-Tenorio A, Álvarez A, Cortés J, Faccini-Martínez ÁA. A case of disseminated intravascular coagulation by leptospirosis during the ongoing yellow fever outbreak in Colombia. New Microbes New Infect 2026 Feb;69:101684.
    doi: 10.1016/j.nmni.2025.101684pubmed: 41492482google scholar: lookup
  4. Bilung LM, Tahar AS, Pui CF, Bakeri MKS, Su'ut L, Ngui R, Kira R, Apun K. Leptospira and Leptospirosis: A Review of Species Classifications, Genomes, Morphological Structures, Antimicrobial Resistances, Transmissions, and Clinical Manifestations. Curr Microbiol 2026 Jan 5;83(2):122.
    doi: 10.1007/s00284-026-04722-7pubmed: 41489657google scholar: lookup
  5. Rosengren P, Johnston L, Ismail I, Smith S, Hanson J. The Characteristics of Patients That Develop Severe Leptospirosis: A Scoping Review. Pathogens 2025 Dec 10;14(12).
    doi: 10.3390/pathogens14121268pubmed: 41471223google scholar: lookup
  6. Sykes A, Smith S, Stratton H, Staples M, Rosengren P, Brischetto A, Vincent S, Hanson J. Lung Involvement in Patients with Leptospirosis in Tropical Australia; Associations, Clinical Course and Implications for Management. Trop Med Infect Dis 2025 Nov 26;10(12).
    doi: 10.3390/tropicalmed10120333pubmed: 41441572google scholar: lookup
  7. Kędzierska-Mieszkowska S, Arent Z. Alternative Sigma Factors of RNA Polymerase as Master Regulators in the Pathogenic Spirochaete Leptospira interrogans. Pathogens 2025 Oct 29;14(11).
    doi: 10.3390/pathogens14111100pubmed: 41305338google scholar: lookup
  8. Di Azevedo MIN, Lilenbaum W. Genetic Diversity and Clonal Expansion of Pathogenic Leptospira in Brazil: A Multi-Host and Multi-Regional Panorama. Microorganisms 2025 Oct 31;13(11).
    doi: 10.3390/microorganisms13112512pubmed: 41304198google scholar: lookup
  9. Tan B, De Vera P, Abrazaldo J, Ng C. Flood-associated disease outbreaks and transmission in Southeast Asia. Front Microbiol 2025;16:1694246.
    doi: 10.3389/fmicb.2025.1694246pubmed: 41199949google scholar: lookup
  10. Timsit JF, Ling L, de Montmollin E, Bracht H, Conway-Morris A, De Bus L, Falcone M, Harris PNA, Machado FR, Paiva JA, Paterson DL, Poulakou G, Roberts JA, Roger C, Shorr AF, Tabah A, Lipman J. Antibiotic therapy for severe bacterial infections. Intensive Care Med 2025 Oct;51(10):1867-1885.
    doi: 10.1007/s00134-025-08063-0pubmed: 40888899google scholar: lookup
  11. Stratton H, Rosengren P, Kinneally T, Prideaux L, Smith S, Hanson J. Presentation and Clinical Course of Leptospirosis in a Referral Hospital in Far North Queensland, Tropical Australia. Pathogens 2025 Jun 28;14(7).
    doi: 10.3390/pathogens14070643pubmed: 40732691google scholar: lookup
Subscribe to our newsletter
Join 99,608 horse owners like you who receive our email updates on horse health and nutrition.